This project examines the function of the salivary glands and other oral tissues in individuals with alterations of normal oral function due to disease or therapeutic procedures. Entry into all studies is through the Dry Mouth Clinic. Utilizing outpatient and inpatient services, specific evaluative and diagnostic approaches establish the cause and extent of salivary gland dysfunction in the "dry mouth" patient. The focus of clinical studies for many years has been primary Sj[unreadable]gren's syndrome, a systemic autoimmune exocrinopathy with major manifestations of chronic, progressive salivary and lacrimal gland dysfunction, and irradiation- induced salivary gland dysfunction. Oral and secretory effects of other selected systemic diseases also are evaluated. An ongoing therapeutic protocol is evaluating the effectiveness of the combination of the anti- inflammatory drug hydroxychloroquine and the parasympathomimetic secretogogue pilocarpine HCl for treatment of salivary, lacrimal, and serological disease in primary Sj[unreadable]gren's syndrome patients. Clinical research studies are I) seeking better salivary and serologic markers of exocrine disease activity in this disorder; ii) defining the expression of adhesion molecules and cytokine receptors in the salivary glands of Sj[unreadable]gren's syndrome patients and normal controls; and iii) evaluating disease progression over time. Laboratory studies focus on the immunopathological mechanisms of salivary dysfunction found in Sj[unreadable]gren's syndrome. Cytokine expression in salivary glands and the effects of cytokines and other immune mediators on a cultured human salivary ductal cell line have been investigated.